Tereza Klučková,Marek Nikolič,Filip Tylš et al. Tereza Klučková et al.

This study examines acute and long-term effects of psilocybin in healthy individuals. Methods: A double-blind, placebo-controlled, cross-over study included 40 healthy participants (20 females, mean age 38)....Each received two doses of psilocybin (0.26 mg/kg) at least 56 days apart (mean 488) in two neuroimaging study arms. Nearly half had previous psychedelic experience....Conclusion: Repeated psilocybin administration in healthy individuals induces positive, lasting effects, with challenging experiences in controlled settings not causing adverse outcomes.

Manish Agrawal,Kim Roddy,Betsy Jenkins et al. Manish Agrawal et al.

Methods: A phase 2 trial was conducted that demonstrated safety, feasibility, and efficacy of a single dose of psilocybin combined with psychological support in a community cancer setting in 30 patients with cancer and a major depressive disorder....Conclusions: These findings demonstrate robust antidepressive activity from a single 25 mg dose of psilocybin combined with psychotherapy and suggest a potentially paradigm-changing alternative to traditional antidepressants requiring further study.

Daniel Hoyer Daniel Hoyer

Classical psychedelics act as 5-HT2A receptor agonists, although LSD, DMT and psilocybin target other 5-HT and/or dopamine receptors. Psychedelic-dependent 5-HT2A receptor agonism also has profound anti-(neuro)inflammatory effects.

Ines Erkizia-Santamaría,Igor Horrillo,Nerea Martínez-Álvarez et al. Ines Erkizia-Santamaría et al.

In the search for novel rapid-acting antidepressants, the psychedelic psilocybin has emerged as a promising therapy in several clinical trials. However, its antidepressant mechanism of action is still not well understood....The aim of the present study was to evaluate the therapeutic potential of psilocybin in ameliorating the adverse behavioural and neurochemical consequences of chronic stress....To this end, a chronic unpredictable mild stress (CUMS) animal model was used, and psilocybin treatment was administered (two doses of 1 mg/kg, i.p., administered 7 days apart)....Furthermore, psilocybin treatment caused a selective increase in the expression of glucocorticoid-receptor (GR) in brain cortex of CUMS mice. In conclusion, psilocybin was able to rescue impairments in the depressive phenotype, and to induce anxiolytic-like effects....Altogether, this work provides new knowledge on the putative benefit/risk actions of psilocybin and contributes to the understanding of the therapeutic mechanism of action of psychedelics. © 2025. The Author(s).

Tom Ben-Tal,Ilana Pogodin,Alexander Botvinnik et al. Tom Ben-Tal et al.

This study investigates the synergistic benefits of combining psilocybin (PSIL) with N-methyl-D-aspartate receptor (NMDAR) modulators D-serine (DSER) and D-cycloserine (DCS) to enhance both efficacy and safety.

Sara Ellis,Catherine Bostian,Anna Donnelly et al. Sara Ellis et al.

This is the first study to evaluate the long-term outcomes of psilocybin in Veterans with severe TRD....Methods: This paper presents 12-month results from an open-label pilot study assessing the effects of 25 mg psilocybin in Veterans with severe TRD, defined as a major depressive episode failing to respond to ≥5 treatments, or lasting >2 years. 10 out of 15 participants completed the...Conclusions: In this first-of-kind study on long-term effects of psilocybin for Veterans with severe TRD, depression scores showed significant sustained reductions up to 12-months.

Alanna Kit,Kate Conway,Savannah Makarowski et al. Alanna Kit et al.

There is growing interest in exploring the therapeutic potential and mechanisms of action of psilocybin on stress-related neuropsychiatric disorders, including depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), addiction, and disordered...Despite promising progressions in preclinical and clinical research, the neurobiological and physiological mechanisms underlying the therapeutic effects of psilocybin remain complex, involving multiple systems with numerous homeostatic feedback signaling pathways throughout the body....This review paper explores how psilocybin mechanistically interacts with the gut microbiota, enteric nervous system, hypothalamic-pituitary axis, and how psilocybin influences the bidirectional communication between peripheral and neuronal systems....Shifting towards a more integrated paradigm to unravel the mechanisms through which psilocybin affects the bidirectional gut-brain axis holds the promise of significantly advancing our understanding of psilocybin-based therapies from preparation of treatment, administration, to proceeding long-term integration

Nadav Liam Modlin,Victoria Williamson,Carolina Maggio et al. Nadav Liam Modlin et al.

Correspondingly, it proposes a conceptual framework for psilocybin treatment in PTSD, framing the condition as a complex, maladaptive interpretive framework that is both predetermined and over-determined....Finally, we offer recommendations for the safe administration of psilocybin for traumatised patients in medical research settings, emphasising the importance of rigorous and trauma-informed protocols and comprehensive patient care....Keywords: PTSD; psilocybin; psilocybin treatment; psychedelic therapy; psychedelics; trauma. © The Author(s), 2025.

Mathieu Fradet,Carlton M Kelly,Anna J Donnelly et al. Mathieu Fradet et al.

Rebecca Harding,Neomi Singer,Matthew B Wall et al. Rebecca Harding et al.